FDA Grants Orphan Drug Status to Lundbeck's Asedebart for Cushing

FDA has granted orphan drug designation to asedebart (Lu AG13909), Lundbeck's investigational anti-adrenocorticotropic hormone (anti-ACTH) monoclonal antibody, for the treatment of endogenous Cushing syndrome, the company announced September 11, 2026.¹ Endogenous Cushing syndrome is a rare endocrine disorder driven primarily by excess ACTH, which leads to chronic cortisol excess and substantial disease burden. Current treatment options are often limited by suboptimal disease control and treatment-related complications.

"The FDA [o]rphan [d]rug [d]esignation is an important step for asedebart and for Lundbeck's growing commitment to rare neuroendocrine disorders," said Tarek Samad, PhD, executive vice president and head of research and development at Lundbeck, in a company press release.¹ "ACTH-dependent Cushing's syndrome can be a devastating condition for patients, with long-term consequences that remain difficult to control despite available treatments. This milestone reflects the strength of the science behind asedebart's development to date and supports our ambition to advance innovative medicines in areas where patients continue to face significant unmet need."

Why is a new treatment needed for ACTH-dependent Cushing syndrome?

ACTH-dependent Cushing syndrome is caused by excess secretion of ACTH, most commonly from a pituitary tumor (Cushing disease) and less often from an ectopic ACTH-secreting tumor. Elevated ACTH drives excess adrenal production of glucocorticoids, mineralocorticoids, and androgens.¹ Sustained cortisol excess contributes to substantial disease burden through metabolic, cardiovascular, and neuropsychiatric complications and is associated with increased morbidity and mortality.¹^,²

Achieving and maintaining adequate disease control can be difficult even with existing medical therapies, which vary in efficacy and may be constrained by safety and tolerability considerations.³ Surgery to remove the source of excess ACTH is the preferred first-line treatment when feasible, but not all patients are eligible or achieve sustained remission.¹

How does asedebart work?

Asedebart is a humanized monoclonal antibody that specifically recognizes ACTH with high affinity, blocking its binding to the melanocortin 2 receptor in the adrenal glands and inhibiting ACTH's neurohormonal signaling, which, in turn reduces adrenal secretion of glucocorticoids, mineralocorticoids, and androgens.¹ A proof-of-concept trial (BalanCeD; NCT06471829) is currently evaluating asedebart's efficacy and safety in Cushing disease. The biologic is also in proof-of-concept testing for classic congenital adrenal hyperplasia (CAH), another rare condition characterized by excess ACTH.¹^,⁴

What other regulatory milestones has asedebart achieved?

This designation follows earlier orphan drug designations for asedebart in the European Union for Cushing syndrome of endogenous origin, as well as prior orphan designations for CAH in the European Union and United States, and for CAH and Cushing disease in Japan.¹ Orphan drug designation is granted by FDA to drugs and biologics intended to treat, diagnose, or prevent rare diseases and may provide development incentives, including tax credits for qualified clinical testing, exemption from certain FDA application fees, and, if approved, up to 7 years of market exclusivity for the designated indication.¹

What are the limitations?

Asedebart is an investigational compound that is not approved for marketing by any regulatory authority worldwide, and its efficacy and safety have not been established. Orphan drug designation provides development incentives but does not necessarily indicate that FDA has evaluated or confirmed the drug's safety or efficacy.

References

1. H. Lundbeck A/S. The US FDA grants orphan drug designation for Lundbeck's investigational anti-ACTH monoclonal antibody asedebart for treatment of endogenous Cushing's syndrome. Press release. Published September 11, 2026. Accessed September 11, 2026. https://www.prnewswire.com/news-releases/the-us-fda-grants-orphan-drug-designation-for-lundbecks-investigational-anti-acth-monoclonal-antibody-asedebart-for-treatment-of-endogenous-cushings-syndrome-302876245.html
2. Nieman LK. Molecular derangements and the diagnosis of ACTH-dependent Cushing's syndrome. Endocr Rev. 2022;43(5):852-877. doi:10.1210/endrev/bnab046
3. Fleseriu M, Auchus R, Bancos I, et al. Consensus on diagnosis and management of Cushing's disease: a guideline update. Lancet Diabetes Endocrinol. 2021;9(12):847-875. doi:10.1016/S2213-8587(21)00235-7
4. A trial of Lu AG13909 in adult participants with Cushing's disease (BalanCeD). ClinicalTrials.gov. NCT06471829. Updated August 21, 2026. Accessed September 11, 2026. https://clinicaltrials.gov/study/NCT06471829